MOLECULAR DESIGN SUPPORT SYSTEM
The present invention generally relates to molecular design support systems for creating or modifying the structure of molecules in a computer by using graphic display function of the computer, and more particularly to a molecular design support system for creating a new molecular structure or modifying an existing molecular structure in a computer by representing the molecular structure in terms of structural components that form the molecular structure.
With the increased computational power of workstations and personal computers, various calculations in the field of theoretical chemistry such as molecular orbital theory, molecular mechanics, molecular dynamics, and the like, are becoming the matter of practical and routine investigation process. In the field of chemistry, material sciences, and pharmaceuticals in particular, such theoretical calculation provides a powerful tool for designing a new molecule. When conducting such a calculation, it is necessary to provide three-dimensional structural data of the molecules or compounds that are subjected to the investigation, to the computer as input data. It is generally known that the reliability of the calculation heavily depends on the quality of the input data supplied to the computer.
In the conventional molecular design support systems, the structural information of molecules are represented in terms of: (a) first data group that represents data about individual atoms forming the molecule such as the type of the atoms (elements) that constitute the molecule, the coordinate and valence of the atoms, and the like; and (b) second data group that represents data about the chemical bond in the molecule such as the identification of the atoms that are connected by the bond, the order of the bond, and the like.
FIGS. 1(A) and 1(B) show an example of the structural information that has been used conventionally, wherein FIG. 1(A) represents the structural formula of acetic acid having the formula CH.sub.3 COOH while FIG. 1(B) shows the structural information of the acetic acid shown in FIG. 1(A). The structural information of FIG. 1(B) is represented in terms of the "mol-file" format proposed by MDL Corporation.
Referring to FIG. 1(B), it will be noted that the first field 1 represents the name and code number of the acetic acid molecule, the second field 2 represents the number of atoms (=8) included in the molecule and the number of bonds (=7) included in the molecule, and the third field 3 represents the atomic data that includes three-dimensional coordinate of the atoms included in the molecule and the type of the atoms or elements forming the molecule. Further, the fourth field 4 identifies each of the atomic pairs forming the chemical bonds in terms of the identification code for identifying the atomic type of the atoms forming the atomic pair and the order of the chemical bond formed therebetween.
The data represented in FIG. 1(B), however, is not convenient for a user to construct a new molecular structure. It should be noted that the procedure for constructing a new molecule includes the steps for specifying the mutual relationship between various structural elements forming the molecular structure. For example, one has to specify the bond length, bond angle, and the torsional angle between various functional groups or constructing a new molecular structure. Obviously, the data shown in FIG. 1(B) is not convenient for such a purpose. On the other hand, such a manual procedure requires expertise of the operator and tends to invite human errors. In addition to the foregoing problems, the process shown in FIG. 1(B) raises another problem in that a very complex processing is necessary when modifying an existing molecular structure such as repeatedly referring to the data in the field 3 and field 4. Thereby, the response of the processing becomes slow and the operation of the system becomes inevitably difficult.
In order to overcome the foregoing problems, it is proposed to prepare in advance the structural data for each of the stable structural components such as fundamental compounds and functional groups and to combine the structural components to form a new molecular structure. By using the sophisticated graphic user interface (GUI) in combination with the foregoing process, one can easily obtain structural data of new molecules. On the other hand, such a process has a drawback in that it requires a preparation of extensive database for the structural components such as the fundamental compounds and functional groups. In addition, it is necessary to determine the bond length, upon substitution of the structural components, with respect to the atomic pair that is formed as a result of the substitution of the structural components. Thereby, the database has to be referred to frequently upon processing, and the time that is needed for the processing becomes inevitably longer.
Alternatively, there is a proposal to bond an atom or an atomic group to an unfilled valence bond of atoms that form a part of the molecule, based upon an empirical law, such that the atom or atomic group is attached automatically by the computer system to an optimum location of the molecule. Although the latter process is simpler to implement for the operator, there is a possibility that the obtained structure may be totally different from the intended structure. This problem tends to occur when arbitrary factors exist in the determination of the structure as in the case where there exists a freely rotatable single-bond associated with low energy barrier or as in the case where there are a plurality of conformations in a ring structure.